A typical rheumatic disease--chronic rheumatoid arthritis (hereinafter RA)--is a systemic connective-tissue disease having a main symptom of polyarthritis chronica, and is one of the autoimmune diseases. The disease type thereof is generally polyarthritis which is progressive and chronic. It includes various clinical types such as one showing spontaneous remission, one showing highly progressive destruction and absorption of joints (e.g., arthritis dissecans) and the like. Clinical symptoms thereof include arthritis, swelling of joint, pain, deformation, morning stiffness, rheumatoid nodule, angiitis and the like.
For internal therapy of RA at present, nonsteroidal antiflammatory agents (e.g., aspirin, indometacin, diclofenac sodium, ibuprofen, loxoprofen sodium, piroxicam, ampiroxicam, naproxen, and the like), adrenocorticosteroidal agents (e.g., intraarticular injection and oral administration of prednisolone, and the like), immunomodulators (e.g., gold preparation, D-penicillamine, bucillamine, actarit and the like), immunosuppressive agents (e.g., methotrexate, mizoribine and the like), and the like are used. These medicaments, nevertheless, fail to provide sufficient therapeutic effects, but rather, cause various side effects. For example, nonsteroidal antiinflammatory agents may cause peptic ulcer, nephropathy, hepatopathy and the like, adrenocorticosteroidal agents may induce and exacerbate infectious diseases, diabetes, moon face, peptic ulcer, adrenocortical insufficiency, thrombophlebitis, osteoporosis and the like, immunomodulators may cause dermatopathy, nephropathy, stomatitis and the like, and immunosuppressive agents may cause hepatopathy, leukopenia, thrombocytopenia and the like, some of which constituting severe side effects.
In view of the above-mentioned situation, there is a demand for the development of an antirheumatic agent effective for the alleviation and suppression of the symptoms of RA and causing fewer side effects.
It is therefore an object of the present invention to provide an antirheumatic agent that is delivered to local sites after oral administration, that is effective for the treatment of RA and that causes fewer side effects.